1. Field of Invention
This invention relates to hybridization of nucleic acids and/or nucleic acid analogues, particularly in the context of genetic diagnostics and therapeutics.
2. Description of Related Art
Although there is a recent report that hybridization efficiency can be enhanced by probes containing hairpins proximal to the target-binding base sequence under certain conditions (Riccelli et al., “Hybridization of single-stranded DNA targets to immobilized complementary DNA probes: comparison of hairpin versus linear capture probes.” Nucleic Acids Res 2001 Feb. 15;29(4):996-1004; see also U.S. Pat. No. 5,770,365 to Lane et al.) it is generally believed that hybridization efficiency is compromised by hairpin formation, wherein a first base sequence of a probe bonds with a second base sequence of the probe complementary to the first base sequence. As a result the probe is less available to complex with target base sequences in the test medium. Single stranded RNA similarly forms hairpins and can therefore be difficult to assay.
While increasing stringency tends to diminish the formation of hairpins, it also diminishes the potential of all hybridization events.
It is the constant preoccupation of researchers to discover means of enhancing binding efficiency of nucleic acids and to mitigate the consequences of unwanted hairpin secondary structure. It is therefore desired to provide such means.
It is further desired to hinder probe hairpin formation while substantially preserving, and preferably enhancing, the sensitivity of the probe for the target base sequence.
All references cited herein are incorporated herein by reference in their entireties.